Abstract：Congenital muscular dystrophy type 1C (MDC1C) is caused by the homozygous or compound heterozygous mutations of the FKRP gene. This article reported the clinical and mutation features of a child with MDC1C. The boy aged 8 months visited the hospital due to delayed development. As for clinical manifestations, the boy could not turn over or sit stably by himself, and there was a significant reduction in muscle tension; biceps reflex in both upper extremities and patellar tendon reflex and Achilles tendon reflex in both lower extremities could not be induced. The boy also had a stereotyped facial expression and strabismus. Gene detection revealed c.350C > G and c.1303C > T compound heterozygous mutations in the FKRP gene. The c.350C > G mutation came from the mother and had been reported as a pathogenic missense mutation. The c.1303C > T mutation came from the father and was a new missense mutation, and a bioinformatics analysis showed that it might be a pathogenic mutation. The boy was diagnosed with MDC1C with reference to the clinical features of hypotonia and motor developmental delay and FKRP gene mutation sequencing.
Topaloglu H., Brockington M, Yuva Y, et al. FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts[J]. Neurology, 2003, 60:988-992.
[2]
Fu X, Yang H, Wei C, et al. FKRP mutations, including a founder mutation, cause phenotype variability in Chinese patients with dystroglycanopathies[J]. J Hum Genet, 2016, 61(12):1013-1020.
[3]
Godfrey C, Foley AR, Clement E, et al. Dystroglycanopathies:coming into focus[J]. Curr Opin Genet Dev, 2011, 21(3):278-285.
[4]
Brockington M, Blake DJ, Prandini P, et al. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha-2 deficiency and abnormal glycosylation of alpha-dystroglycan[J]. Am J Hum Genet, 2001, 69(6):1198-1209.
[5]
Esapa CT, Benson MA, Schröder JE, et al. Functional requirements for fukutin-related protein in the Golgi apparatus[J]. Hum Mol Genet, 2002, 11(26):3319-3331.
[6]
Kanagawa M, Kobayashi K, Tajiri M, et al. Identification of a post-translational mod ification with ribitol-phosphate and its defect in muscular dystrophy[J]. Cell Rep, 2016, 14(9):2209-2223.
[7]
Ibraghimov-Beskrovnaya O, Ervasti JM, Leveille CJ, et al. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix[J]. Nature, 1992, 355(6362):696-702.
[8]
Sato S, Omori Y, Katoh K, et al. Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation[J]. Nat. Neurosci, 2008, 11(8):923-931.
[9]
Ervasti JM, Campbell KP. A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin[J]. J Cell Biol, 1993, 122(4):809-823.
[10]
Mercuri E, Brockington M, Straub V, et al. Phenotypic spectrum associated with mutations in the fukutin-related protein gene[J]. Ann. Neurol, 2003, 53(4):537-542.
[11]
Topaloglu H, Brockington M, Yuva Y, et al. FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts[J]. Neurology, 2003, 60(6):988-992.
[12]
Louhichi N, Triki C, Quijano-Roy S, et al. New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities. Identification of a founder mutation in Tunisian families[J]. Neurogenetics, 2004, 5(1):27-34.
[13]
Mercuri E, Topaloglu H, Brockington M, et al. Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations[J]. Arch Neurol, 2006, 63(2):251-257.
[14]
Esapa CT, McIlhinney RA, Blake DJ. Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells[J]. Hum Mol Genet, 2005, 14(2):295-305.
[15]
Yoshioka M, Kobayashi K, Toda T. Novel FKRP mutations in a Japanese MDC1C sibship clinically diagnosed with Fukuyama congenital muscular dystroph[J]. Brain Dev, 2017, 39(10):869-872.
[16]
Taniguchi-Ikeda M, Morioka I, Iijim K, et al. Mechanistic aspects of the formation of α-dystroglycan and therapeutic research for the treatment of α-dystroglycanopathy:A review[J]. Mol Aspects Med, 2016, 51:115-124.
